Process for preparing 3-deacetylate-7-aminocephalosporanic acid

A technology for aminocephalosporanic acid and deacetylation, applied in the field of medicine, can solve the problems of long process route, increase production cost, consume energy and the like, and achieve the effects of reducing environmental pollution, increasing production cost and reducing production cost

Active Publication Date: 2012-01-18
石药集团内蒙古中诺药业有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Among the above-mentioned preparation methods, the chemical method and the chemical-biological enzymatic method have a long process route, and all have to undergo three crystallization processes of cephalosporin C sodium salt (or zinc salt), 7-ACA, and D-7-ACA. Due to the crystallization process, product loss Many, resulting in low yield of the method
In addition, the cracking used in the chemical method requires high temperature, high pressure and low cooling, and the organic solvents used in the reaction materials, such as dichloromethane, aniline, and chlorosilane, are poisonous and harmful pollutants, and a large amount of strong acid and alkali are used. The production of D-7-ACA has to bear heavy energy consumption costs and pollution control costs
In the chemical and biological enzymatic method, 7-ACA is first prepared by enzymatic method, and then chemically or enzymatically cleaved

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] a. Weigh 4.2KU cephalosporin acylase, wash with anhydrous salt water, and put it into a 2.0L enzyme reactor;

[0033] b. Take the 3-deacetyl cephalosporin C nanofiltration concentrated liquid analyzed by sodium bicarbonate with a concentration of 55.6g / L and prepare 1.2L of 3-deacetyl cephalosporin C with a concentration of 35.1g / L with anhydrous salt water The solution was put into a 2.0L enzyme reactor, the stirring speed was 400rpm, the pH was controlled to be 8.05 with 3mol / L ammonia water, and the temperature was 18°C. After reacting for 80min, the reaction solution was transferred to a 2L beaker (cephalosporin acylase was sieve at the bottom of the enzyme reactor);

[0034] c. Cool the reaction solution to 5°C, add 10% hydrochloric acid dropwise to adjust the pH to 5.75, let it grow for 30 minutes, then continue to add hydrochloric acid to pH 4.04, grow the crystal for 4 hours, filter with suction, wash twice with 100ml of water, and use 100ml of Washed twice w...

Embodiment 2

[0036] a. Weigh 7.8KU cephalosporin acylase, wash with anhydrous salt water, and put it into a 2.0L enzyme reactor;

[0037] b. Take the concentrated solution of 3-deacetyl cephalosporin C analyzed by ammonium acetate with a concentration of 50.3g / L and prepare 1.2L of 3-deacetyl cephalosporin C solution with an anhydrous concentration of 43.2g / L, and put it into In a 2.0L enzyme reactor, the stirring speed is 400rpm, the pH is controlled to be 8.3 with 3mol / L ammonia water, the temperature is 20°C, and after 80 minutes of reaction, the reaction solution is transferred to a 2L beaker (cephalosporin acylase is absorbed by the enzyme reactor bottom screen retention);

[0038] c. Cool the reaction solution to 5°C, add 10% hydrochloric acid dropwise to adjust the pH to 5.80, let it grow for 30 minutes, then continue to add hydrochloric acid to pH 4.03, grow the crystal for 4 hours, filter with suction, wash twice with 100ml of water, and use 100ml of Washed twice with 1:1 aceto...

Embodiment 3

[0040] a. Weigh 10KU of cephalosporin acylase, wash it with anhydrous salt water, and put it into a 2.0L enzyme reactor;

[0041]b. get the 3-deacetyl cephalosporin C concentrated solution that the ammonium acetate of 89.7g / L resolves and prepare 1.2L concentration of 3-deacetyl cephalosporin C that is 49.7g / L with anhydrous salt, drop into In a 2.0L enzyme reactor, the stirring speed is 400rpm, the pH is controlled to 8.50 with 3mol / L ammonia water, the temperature is 25°C, and after 100min of reaction, the reaction solution is transferred to a 2L beaker (cephalosporin acylase is absorbed by the bottom of the enzyme reactor) sieve retention);

[0042] c. Cool the reaction solution to 5°C, add 10% hydrochloric acid dropwise to adjust the pH to 6.01, let it grow for 30 minutes, then continue to add hydrochloric acid to pH 4.12, grow the crystal for 4 hours, filter with suction, wash twice with 100ml of water, and use 100ml of 1:1 acetone washed twice, dried at 50°C for 3 hou...

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PUM

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Abstract

The invention discloses a process for preparing 3-deacetylate-7-aminocephalosporanic acid, belonging to the technical field of medicines. The method disclosed by the invention comprises the following steps of: directly catalyzing 3-deacetylate cephalosporin C extract with cephalosporin acylase, then acidifying and crystallizing, washing and drying to obtain solid 3-deacetylate-7-aminocephalosporanic acid. The method only requires one-step normal temperature cracking reaction and one crystallizing process, process rout is short, pollution is less, mole yield of product is more than 86%, and the method disclosed by the invention is applicable to industrialization production.

Description

technical field [0001] The invention relates to a preparation process of a pharmaceutical intermediate, in particular to a preparation process of 3-deacetyl-7-aminocephalosporanic acid, which belongs to the technical field of medicine. Background technique [0002] 3-deacetyl-7-aminocephalosporanic acid is called D-7-ACA for short. Because the amino group at the 7th position and the hydroxyl group at the 3rd position are relatively active, different side chains can be introduced to synthesize a series of cephalosporin antibiotics, such as cephalosporin Cefuroxime, Cefuroxime, Cefpirome, Cefcapene Proxetil, Cefdinir, Ceftazidime, etc. With the increase in the amount of cephalosporin antibiotics and the development of new cephalosporin antibiotics, the demand for D-7-ACA in pharmaceutical production is also increasing. [0003] At present, there are three main methods for preparing D-7-ACA: chemical method, chemical-biological enzymatic method and biological enzymatic method,...

Claims

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Application Information

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IPC IPC(8): C12P35/02
Inventor 卢华袁国强朱科王艳艳丁海平薛瀚孟德程延国东王进贤刘萌
Owner 石药集团内蒙古中诺药业有限公司
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